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Introduction Growth Differentiation Factor-15 (GDF-15) has emerged as a novel marker in gyne-cological cancers. But its suitability in clinical diagnostics is yet to be recognized. Materials and methods We sorted out eligible studies from multiple online databases like Pubmed, Cochrane, ClinicalTrials.gov, Google Scholar, Web of Science, Embase, Scopus, LILACS, and Opengrey. The terms used were ‘Growth Differentiation Factor-15’, ‘GDF-15’, ‘Macrophage Inhibitory Cytokine-1’, ‘MIC-1’, ‘Ovarian cancer’, ‘Ovarian carcinoma’, ‘Endometrial cancer’, ‘Endometrial carcinoma’, ‘Uterine cancer’, ‘Uterine Carcinoma’, ‘Cervical cancer’, ‘Cervical car-cinoma’, ‘diagnosis’, ‘sensitivity’, ‘specificity’, ‘prognosis’, and ‘outcome’. Of the full-text, potentially eligible records, six were found eligible for inclusion into our meta-analysis. Studies were selected only if the diagnosis was proven by pathology, cases recruited were those without any prior treatment, sufficient diagnostic accuracy data were present for GDF-15 in gynecological cancers, ethical approval was taken from Institutional Ethics Committee, and full-text material was available in English. Nonclinical research and animal studies were excluded. We took the assistance of the Rayyan QCRI software for the screening and selection process. We conducted the study following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and used Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) to assess the risk of bias. The protocol was registered at PROSPERO, registration number CRD42019130097. Results We extracted diagnostic accuracy data from the articles and evaluated the role of GDF-15 by pooling the sensitivity, specificity, and diagnostic odds ratio (DOR) and plotting a summary receiver operating characteristic (SROC) curve. Since there was heterogeneity across the studies, random-effects model was employed to carry out the integration. The meta-analysis showed that GDF-15 has a pooled DOR of 12.74 at 80.5% sensitivity and 74.1% specificity, with an area under the curve (AUC) of 0.84. Conclusion Our analysis suggests that GDF-15 may be a useful candidate marker to differentiate malignant from non-malignant tumors of the female reproductive system. Registration detail: PROSPERO, CRD42019130097.

Axillary nodal metastasis is related to poor prognosis in breast cancer (BC). Key candidate genes in BC lymph node metastasis have been identified from Gene Expression Omnibus datasets and explored through functional enrichment database for annotation, visualization and integrated discovery (DAVID) , protein-protein interaction by Search Tool for the Retrieval of Interacting Genes and proteins (STRING), network visualization (Cytoscape), survival analysis (GEPIA, KM Plotter), and target prediction (miRNet). A total of 102 overlapping differentially expressed genes were found. In-silico survival and expression analyses revealed six candidate hub genes, Desmocollin 3 (DSC3), KRT5, KRT6B, KRT17, KRT81, and SERPINB5, to be significantly associated with nodal metastasis and overall survival, and 83 MicroRNA (miRNAs), which may be potential diagnostic markers and therapeutic targets in BC patients.

COVID-19 has emerged as a global pandemic. It is mainly manifested as pneumonia which may deteriorate into severe respiratory failure. The major hallmark of the disease is the systemic inflammatory immune response characterized by Cytokine Storm (CS). CS is marked by elevated levels of inflammatory cytokines, mainly interleukin-6 (IL-6), IL-8, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Of these, IL-6 is found to be significantly associated with higher mortality. IL-6 is also a robust marker for predicting disease prognosis and deterioration of clinical profile. In this review, the pivotal role played by IL-6 in the immuno-pathology of COVID-19 has been illustrated. The role of IL-6 as a pleiotropic cytokine executing both pro and anti-inflammatory activities has been reviewed. ADAM 10, a metalloproteinase switches the anti-inflammatory pathway of IL-6 to pro inflammatory hence blocking the action of ADAM 10 could be a new therapeutic strategy to mitigate the proinflammatory action of IL-6. Furthermore, we explore the role of anti-IL6 agents, IL-6 receptor antibodies which were being used for autoimmune diseases but now are being repurposed for the therapy of COVID-19.

COVID-19 has similarities to the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, as severe patients and non-survivors have frequently shown abnormal coagulation profiles. Immune-mediated pathology is a key player in this disease; hence, the role of the complement system needs assessment. The complement system and the coagulation cascade share an intricate network, where multiple mediators maintain a balance between both pathways. Coagulopathy in COVID-19, showing mixed features of complement-mediated and consumption coagulopathy, creates a dilemma in diagnosis and management.Pathophysiology of coagulopathy in COVID-19 patients, with a particular focus on D-dimer and its role in predicting the severity of COVID-19 has been discussed. A comprehensive search of the medical literature on PubMed was done till May 30th, 2020 with the keywords 'COVID-19', 'SARS-CoV-2', 'Coronavirus', 'Coagulopathy', and 'D-dimer'. Twenty-two studies were taken for weighted pooled analysis of D-dimer.A tailored anticoagulant regimen, including intensification of standard prophylactic regimens with low-molecular-weight heparin is advisable for COVID-19 patients. Atypical manifestations and varying D-dimer levels seen in different populations bring forth the futility of uniform recommendations for anticoagulant therapy. Further, direct thrombin inhibitors and platelet inhibitors in a patient-specific manner should also be considered.

Galectins are defined as the glycan-binding protein containing either one or two carbohydrate-binding domains and participate in various biological functions such as developmental processes, vascularisation programs, cell migration, and immune-regulation and apoptosis. Galectins are also linked to many diseases, including cancer. They are widely spread in extracellular and intracellular spaces, and their altered expression in cancer leads to tumor progression, metastasis, angiogenesis and stemness through different signalling pathways. Promoter methylation, microRNA, and histone modification constitute the epigenetic changes that regulate galectin activity in cancer. Our review discusses the concept of epigenetics in cancer and how the aforementioned factors i.e., promoter methylation, histone modification, change in miRNAs expression affect the glycomic changes in malignancies.

Breast cancer is recognized for its different clinical behaviors and patient outcomes, regardless of common histopathological features at diagnosis. The heterogeneity and dynamics of breast cancer undergoing clonal evolution produces cells with distinct degrees of drug resistance and metastatic potential. Presently, single cell analysis have made outstanding advancements, overshadowing the hurdles of heterogeneity linked with vast populations. The speedy progression in sequencing analysis now allow unbiased, high-output and high-resolution elucidation of the heterogeneity from individual cell within a population. Classical therapeutics strategies for individual patients are governed by the presence and absence of expression pattern of the estrogen and progesterone receptors and human epidermal growth factor receptor 2. However, such tactics for clinical classification have fruitfulness in selection of targeted therapies, short-term patient responses but unable to predict the long-term survival. In any phenotypic alterations, like breast cancer disease, molecular signature have proven its implication, as we aware that individual cell's state is regulated at diverse levels, such as DNA, RNA and protein, by multifaceted interplay of intrinsic biomolecules pathways existing in the organism and extrinsic stimuli such as ambient environment. Thus for complete understanding, complete profiling of single cell requires a synchronous investigations from different levels (multi-omics) to avoid incomplete information produced from single cell. In this article, initially we briefed on novel updates of various methods available to explore omics and then we finally pinpointed on various omics (i.e. genomics, transcriptomics, epigenomics, proteomics and metabolomics) data and few special aspects of circulating tumor cells, disseminated tumor cells and cancer stem cells, so far available from various studies that can be used for better management of breast cancer patients.

Background Coronavirus disease 2019 is characterized by the elevation of a broad spectrum of inflammatory mediators associated with poor disease outcomes. We aimed at an in-silico analysis of regulatory microRNA and their transcription factors (TF) for these inflammatory genes that may help to devise potential therapeutic strategies in the future. Methods The cytokine regulating immune-expressed genes (CRIEG) were sorted from literature and the GEO microarray dataset. Their co-differentially expressed miRNA and transcription factors were predicted from publicly available databases. Enrichment analysis was done through mienturnet, MiEAA, Gene Ontology, and pathways predicted by KEGG and Reactome pathways. Finally, the functional and regulatory features were analyzed and visualized through Cytoscape. Results Sixteen CRIEG were observed to have a significant protein-protein interaction network. The ontological analysis revealed significantly enriched pathways for biological processes, molecular functions, and cellular components. The search performed in the miRNA database yielded ten miRNAs that are significantly involved in regulating these genes and their transcription factors. Conclusion An in-silico representation of a network involving miRNAs, CRIEGs, and TF, which take part in the inflammatory response in COVID-19, has been elucidated. Thus, these regulatory factors may have potentially critical roles in the inflammatory response in COVID-19 and may be explored further to develop targeted therapeutic strategies and mechanistic validation.

Background: Diabetic Nephropathy (DN), a microvascular complication, is a major cause of end-stage renal disease (ESRD). GDF-15 and hsa-miR-21 are closely associated with endothelial dysfunction and inflammation.Methods: In-silico analysis was used to identify GDF-15 and insulin related protein-protein interaction (PPI) network and a common set of GDF-15 regulating transcription factors. Common targeting miRNA of GDF-15 regulating transcription factors were investigated in miRNet and TargetScan. Further, 30 type 2 DN patients and 30 healthy controls were included for clinical chemistry analysis, to analyze serum GDF-15 levels by ELISA and to evaluate the fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR.Results: In the PPI network of IRS1, IRS2, INSR, IGF1R, INS, AKT1, PPARG, CEBPB, EGR1, TP53, KLF4, ATF3, GDF15, TWIST2, the common nodes between insulin and GDF-15 were identified. MicroRNA-21 was bioinformatically observed to directly target GDF-15 downregulating transcription factors KLF4, TP-53, and CEBPB. Serum GDF-15 was nearly ten (10) folds higher in DN patients (p˂0.0001) as compared to healthy controls. A positive and significant correlation of serum GDF-15 was found with HbA1c, HOMA-IR, serum urea and serum creatinine. The FCE of hsa-miR-21 was 9.18 folds higher in DN patients. Conclusion: Raised serum GDF-15 and circulating hsa-miR-21 can serve as clinically important therapeutic targets and biomarkers of progressive renal disorder.

Acute kidney injury (AKI), characterised by fluid imbalance and overload, is prevalent in severe disease phenotypes of coronavirus disease 2019 (COVID-19). The elderly immunocompromised patients with pre-existing comorbidities being more risk-prone to severe COVID-19, the importance of early diagnosis and intervention in AKI is imperative. Histopathological examination of COVID-19 patients with AKI reveals viral invasion of the renal parenchyma and evidence of AKI. The definitive treatment for AKI includes renal replacement therapy and renal transplant. Immunosuppressant regimens and its interactions with COVID-19 have to be further explored to devise effective treatment strategies in COVID-19 transplant patients. Other supportive strategies for AKI patients include hemodynamic monitoring and maintenance of fluid balance. Antiviral drugs should be meticulously monitored in the management of these high-risk patients. We have focussed on the development of renal injury provoked by the SARS-CoV-2, the varying clinical characteristics, and employment of different management strategies, including renal replacement therapy, alongside the emerging cytokine lowering approaches.

Oral Squamous Cell Carcinoma (OSCC) is common preventable disease when diagnosed early, but mostly its progression follows transition from oral potentially malignant disorders (OPMDs) like Oral Submucous Fibrosis (OSF). However, it is difficult to predict possibilities of progression in these premalignant lesions hence, identification of molecular biomarkers would have major clinical impact in early diagnosis and better prognosis. In this context microRNA’s(miR’s) provide better opportunities in malignancy prediction and demarcation in OSF to OSCC transition as they perform key regulatory roles in many tumorigenic processes. Here, we computationally screened differentially expressed miR’s of OSCC and OSF from public databases followed by construction of protein interaction networks and enrichment analyses. The relevant miR’s were validated using qPCR of total 93 samplesincluding 34 OSCC, 30 OSF and 29 control blood and tissue samples. We identified significant down regulation of miR-133a-3p in OSCC compared to controls and interesting up-regulation compared to OSCC and control. miR-9-5p was up-regulated in OSF as well as OSCC and down-regulated in OSF compared to OSCC. Therefore, these two miR’s may serve as risk stratification biomarkers with validation in larger categorical datasets.

Background: Type 2 diabetes mellitus (T2DM) is an ever-growing epidemic in India, and poses significant morbidity, mortality, and socioeconomic burden. Introduction: Growth differentiation factor-15 (GDF15) is a stress-responsive cytokine, increased in T2DM patients compared to control subjects without the disease. We aimed to assess whether serum GDF15 and adipose tissue GDF15 expression can differentiate between obese pre-diabetes and T2DM and control populations. Methodology: We recruited 156 individuals including 73 type 2 diabetes, 30 pre-diabetes, and 53 healthy controls. Clinical history, anthropometric measurements and biochemical profiling were done. Insulin resistance indices were calculated following HOMA models. Serum GDF15 was measured by sandwich ELISA. Visceral adipose tissue (VAT) expression of GDF15 was observed in 17 T2DM patients and 29 controls using SYBR Green chemistry in RT-PCR using GAPDH as housekeeping gene. The data were analyzed on R programming platform using RStudio. Results: Serum GDF15 was significantly higher (p Conclusion: Hence, serum GDF15 is a biomarker for T2DM patients in our study population from Western India. However, larger prospective cohorts are necessary to validate this claim.

Background and Aims Metabolic syndrome (MS) is found to be prevalent in patients with mental illness including depression. Data is sparse on the role of lifestyle factors on MS in depression. Methods This study was aimed to assess correlates of MS in patients with depression. Methodology: Three hundred eighty-two patients with depressive disorders were assessed for the prevalence of MS by using modified National Cholesterol Education Program- Adult Treatment Panel-III criteria (NCEP ATP-III). Their illness severity, functionality, physical activity and nutritional habits were also assessed. Conclusions Majority of patients with depression (82.2%) were drug naive. One-fourth of the patients had metabolic syndrome (27.7%). Additionally, other 59% of patients had one or two metabolic abnormalities and one-third of patients were obese. Lower high density lipoprotein cholesterol level was the most common abnormality (65%), while abnormal blood pressure was the least common abnormality (18%). Significant correlates of MS were greater age, and age at onset of depression, greater illness duration, lesser physical activity and lower nutritional score. Conclusion Nearly one-fourth of patients with depression had MS; another three-fifth of patients had one or two metabolic abnormalities. MS was more commonly seen with sedentary lifestyle and poor nutritional habits. It calls for comprehensive assessment and timely management of cardiovascular risk factors as well as lifestyle factors in depression.

Obesity increases the risk of the development of several malignancies. The visceral adipose tissue (VAT) depot is one of the pivotal contributors behind the obesity-related pathogenetic mechanisms. In this study, we analyzed the differential gene expression profile in the VAT of obese children using two Gene Expression Omnibus datasets. GSE29718 and GSE9624 were sorted and 68 common differentially expressed genes (DEG) with fold change 1.5 upregulation or downregulation (cutoff |logFC|≥0.58496) were obtained. Gene ontology and functional enrichment and protein-protein interaction (PPI) network for the DEG were analyzed in Search Tool for the Retrieval of Interacting Genes (STRING), which revealed 37 biological processes, 3 cellular components, and 1 molecular function to be significantly associated. Reactome pathway analysis showed the DEG to be involved in- one carbon pool by folate, glycine degradation, transcriptional regulation by TP53, ERK inactivation, G1/S-specific transcription, Fanconi anemia pathway, beta-catenin phosphorylation cascade, RAF activation, and negative regulation of the MAPK pathway. The PPI network was set with a minimum interaction score of 0.400 and a maximum of 10 interactions, and it was significantly enriched (p-value 0.047) with 66 nodes and 46 edges. Target prediction was performed using miRNet. Several miRNA, including hsa-miR-1-3p, hsa-let-7b-5p, hsa-miR-16-5p, hsa-miR-27a-3p and hsa-miR-34a-5p were part of the mRNA-miRNA interaction network. Using the CytoHubba plugin in Cytoscape, the top 10 hub genes from the PPI network were discovered. Thymidine phosphorylase (TYMP) and dihydrofolate reductase (DHFR), essential components of nucleic acid metabolism, have been shown to be involved in angiogenesis and endothelial cell growth, and correlated to p53 mutations, respectively. Protein phosphatase 2, regulatory subunit A & regulatory subunit B (PPP2R1A and PPP2R1B) mutations are involved in ovarian, endometrial, lung and colorectal cancers. HLA-DQA1 mutation is involved cervical cancer, and it is involved in increased immune sensitivity and liver damage in breast cancer patients. The RAB7Ab and RAB7-interacting lysosomal protein (RILP) are regulators of endo-lysosomal trafficking and suppresses breast cancer cell invasion. To conclude, this study identifies several genes and their regulatory pathways in VAT which may contribute to the increased risk of cancer pathogenesis in obese individuals.

Lead toxicity is a major public health issue in developed and developing countries. Both acute and chronic lead exposure has the potential to cause many deleterious systematic effects including hypertension, frank anemia, cognitive deficits, infertility, immune imbalances, delayed skeletal and deciduous dental development, vitamin D deficiency, and gastrointestinal effects. The underlying mechanisms for all these systemic effects have not been elucidated completely. However, the most plausible cause is free radical damage. In addition to this, lead being a divalent cation can surrogate for calcium at multiple levels affecting various cell signaling pathways. The molecular basis of lead exposure resulting in various systemic effects is being extensively explored. The reports include single nucleotide polymorphisms, epigenetic modifications in susceptible individuals, and the most recent reports also feature regulatory RNA molecules - miRNAs. However, many genetic targets are identified, but their possible mechanisms are still an area to be explored. Additional studies are needed in different population groups to validate the existing findings, as well as to find newer targets that may help in better understanding the molecular mechanisms contributing to lead toxicity. Furthermore, newer strategies for lead risk assessment becomes necessary as the previously recognized "safe" level of lead is also being found to be associated with negative health outcomes.

Background: Diabetes Mellitus is a multifactorial disease encompassing various pathogenic pathways. To avoid morbidity and mortality related to diabetic complications, early detection of disease complications as well as targeted therapeutic strategies are essential. Introduction: MicroRNAs (miRs) are short non-coding RNA molecules that regulate eukaryotic posttranscriptional gene expression. MicroRNA-21 has diverse gene regulatory functions and plays a significant role in various complications of Type 2 diabetes mellitus (T2DM). Methods: The study included electronic database searches on Pubmed, Embase, and Web of Science with the search items MicroRNA21 and each of the diabetic complications. The search was carried out up to November, 2019. Results: MicroRNA-21 modulates diabetic cardiomyopathy by affecting vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. At the renal tubules, miR-21 can regulate the mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria and fibrotic and inflammatory gene expression related to diabetic nephropathy. Overexpression of miR-21 has been seen to play a pivotal role in the pathogenesis of diabetic retinopathy by contributing to diabetes-induced endothelial dysfunction as well as low-grade inflammation. Conclusion: Considering the raised levels of miR-21 in various diabetic complications, it may prove to be a candidate biomarker for diabetic complications. Further, miR-21 antagonists have shown great potential in the treatment of diabetic cardiomyopathy, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy related complications in the future. The current review is the first of its kind encompassing the roles miR-21 plays in various diabetic complications, with a critical discussion of its future potential role as a biomarker and therapeutic target.

OBJECTIVE: Acute lower respiratory infections are an important cause of morbidity and mortality in developing countries. Recent randomized trials of zinc supplementation for the prevention of acute lower respiratory tract infections have revealed discrepant findings. The main aim of this study was to evaluate the prevalence of zinc deficiency and the effect of zinc supplementation on respiratory infections. MATERIAL AND METHODS: A single center, prospective open-label interventional single-arm pre-post study of the effect of oral zinc supplementation in zinc deficient children aged 6 months to 5 years was done. A total of 465 healthy children of age 6 months to 5 years were enrolled in the study for estimation of the prevalence of zinc deficiency. Children having zinc deficiency were recruited to study the efficacy and safety of oral administration of 20 mg zinc for two weeks during a 6-month follow-up period. RESULTS: There were statistically significant differences between the zinc deficient and non-deficient groups according to modified Kuppuswamy categorization of family status and exclusive breast feeding. There was significant difference in the mid arm circumference between the zinc deficient and non-deficient groups (p

Ovarian cancer is a heterogeneous disease that influences women worldwide, is diagnosed at an advanced stage in most patients, and has no effective screening tests for initial detection. The incidence of this cancer is 225,500 diagnoses per year worldwide, and it is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis. Therefore, better management strategies are needed to improve outcomes for women with advanced ovarian cancer.

The dynamics and heterogeneity of breast cancer undergoing clonal evolution produce cells with varying degrees of drug resistance and metastatic potential. Breast cancer is well known for different clinical behaviors and patient outcomes, in spite of common histopathological features at diagnosis. Currently, single-cell analysis has made remarkable advances, overshadowing the problem of heterogeneity linked with huge populations. Rapid progression in sequencing methods now permits unbiased, high-output, and high-resolution interpretation of heterogeneity from individual cells within a population. Conventional treatment strategies for individual patients are directed by the presence and absence of expression pattern of the estrogen and progesterone receptors (ER and PR) and human epidermal growth factor receptor 2 (HER2). Though such approaches for clinical classification have usefulness in selection of targeted therapies and short-term patient responses, they are unable to predict long-term survival. In any phenotypic alterations, like breast cancer disease, the molecular signature has proven its significance, as we know that an individual cell's state is controlled at diverse levels, such as DNA, RNA, and protein, by a multifaceted interplay of intrinsic biomolecule pathways existing in the organism and extrinsic stimuli such as the ambient environment. Thus for comprehensive understanding, complete profiling of a single-cell requires synchronous investigations from different levels (multiomics) to circumvent incomplete information produced from single-cells. In this chapter, initially we present current updates on the various methods available to explore omics and then we focus on omics (i.e., genomics, transcriptomics, epigenomics, proteomics, and metabolomics) data available from various studies that can be used for better management of breast cancer patients.

Objective: COVID-19 has emerged as a multi-system disease with the potential for endocrine dysfunction. We aimed to study the hormonal profile of hospitalized patients with COVID-19 at a tertiary care referral hospital at Jodhpur, India. Design: A hospital-based clinical study of endocrine profile of COVID-19 patients conducted from 15th May to 30th June 2020 after ethical approval. Measurements: Fasting blood samples for free thyroxine (T4), free tri-iodothyronine (T3), thyroid stimulating Hormone (TSH), serum prolactin; basal and 1 h post-intramuscular adrenocorticotropic hormone (ACTH) stimulated cortisol, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were collected within 24 h of admission after written informed consent. All hormones and IL-6 were analyzed by chemiluminescent immunoassay. hsCRP was measured by immune-turbidimetric assay. Results: Of 235 patients studied, 14% had severe disease and 5.5% died. Adrenal insufficiency was present in 14%, most of whom had mild disease. A robust adrenal response was observed in those with severe disease. Basal and post-ACTH serum cortisol were significantly increased in severe disease or those who died compared to those who were mild or asymptomatic. Basal and post-ACTH serum cortisol showed a significant positive correlation with hsCRP but not with IL-6. Low T3 and low T4 syndrome were documented in 25% and 5%, respectively. Serum TSH and FT3 levels declined significantly from asymptomatic to severe category. Hyperprolactinemia was found in 21 patients. hsCRP showed a rising trend with disease severity while IL-6 did not. Conclusions: Endocrine dysfunction in the form of adrenal insufficiency, low T3, and low TSH syndrome and hyperprolactinemia were common COVID-19 hospitalized patients.

Animal models of depression have reported elevated levels of T helper 17 (Th17) and T helper 1 (Th1) cells along with a decrease in T regulatory (Treg) cell percentage. However, there is ambiguity in the results of clinical studies investigating Th17 cells in Major Depressive Disorder (MDD). No studies have investigated the role of Interferon gamma positive Th17 cells (IFNγ+ Th17) in MDD yet.The study population included 53 patients of first episode, drug naïve MDD patients, and 53 non-psychiatric healthy volunteers as healthy controls. Th17, Th1, IFNγ+ Th17 and Treg cell percentages were assessed by flow cytometry.The mean (±SD) percentage of Th17 cells in cases (1.87 ± 1.03) was significantly higher than the mean in controls (1.1 ± 0.94) (p 0.001). There was no significant difference in the Treg percentages between the cases (2.1 ± 2.0) and controls (2.23 ± 0.95). The Th17:Treg ratio was significantly higher in cases (5.41 ± 10.84) compared to the controls (0.69 ± 0.89) (p 0.05). Further analysis of data has also revealed that IFNγ+ Th17 subsets secreted more IL-17 in cases (515.7 ± 423.4) compared to controls (509.6 ± 337.4). Intracellular IL-17 levels in this subset also showed a weak though insignificant positive correlation with HDRS scores in the cases.Elevated circulating Th17 cell percentage and Th17:Treg ratio in MDD cases thus add to the evidence suggesting Th17 mediated pro-inflammatory state in MDD. The study also provides preliminary findings of the more pathogenic IFNγ+ Th17 cell subset in MDD.

Hypocalcemia is a laboratory and clinical abnormality that is observed especially in neonates and paediatric patients. Laboratory hypocalcaemia is often asymptomatic but it can manifest as central nervous system irritability, paraesthesia, tetany (i.e. contraction of hands, arms, feet, larynx, bronchioles), seizures, and even psychiatric changes in children. Cardiac function may also be impaired because of poor muscle contractility. We report a unique case of an eleven year old male child who presented with chronic kidney disease associated with severe hypocalcemia, tonic-clonic seizures, hypovitaminosis D but normal electroencephalogram and electrocardiography. The child required prolonged intravenous calcium gluconate therapy to correct his ionised calcium levels.

Background: Routine zinc supplementation is a potential intervention for the prevention of acute lower respiratory infections in developing countries. However discrepant findings from recent randomized trials remain unexplained. Methods: Single centre, single arm, prospective non-randomized, open label interventional study, of effect of zinc supplementation in zinc deficient children aged 6 months to 5 years. 465 healthy children aged 6 months to 5 years were enrolled in the study. The primary outcome was the prevalence of serum zinc deficiency. Children having zinc deficiency were recruited for the study of effect of oral administration of zinc 20 mg for 2 weeks. The secondary outcomes were incidence and duration of acute upper respiratory and acute lower respiratory infections per child-year and side effects after giving zinc therapy. Results: There was significant difference in mid arm circumference in between zinc deficient and non-zinc deficient groups (p < 0.001). Also the number of episodes of acute upper respiratory infections (AURI) and mean duration of AURI and acute lower respiratory infections (ALRI) was significantly different in the two groups (p < 0.001). There was no significant difference in ALRI episodes in two groups. After zinc supplementation in zinc deficient children, there was significant decrease in the number of episodes and mean duration of AURI (p < 0.001) and ALRI (p < 0.001) in six months after supplementation as compared to preceding six months before supplementation. Conclusion: This study sheds light on the efficacy of short course prophylactic zinc supplementation in reducing the burden of ARI among zinc deficient children. Future studies should assess the effectiveness of delivering prophylactic zinc supplementation at scale, comparing the feasibility and cost benefit of short course and continuous regimens. Clinical Trial Number: As it was a Non Randomized observational single arm study, study was not registered. Only RCT needs to be registered. Funding Statement: This study was funded by All India Institute of Medical Sciences (AIIMS), Manuscript Jodhpur, India, as a part of Intramural project conducted in the department of Pediatrics, AIIMS Jodhpur. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study was approved by Institutional Ethics committee of All India Institute of Medical Sciences, Jodhpur, India. The study was conducted in accordance with ICH-GCP and other applicable regulatory guidelines.

Polycystic ovarian syndrome (PCOS) is one of the commonest endocrine pathies in women of reproductive age. We aimed to establish cardiovascular (CVD) risk factors in pre-menopausal Indian women with PCOS. Methods and Results: Study included 150 women (100 PCOS and 50 controls) from reproductive age (25-45 years). Both study groups were examined and analysed for anthropometric, clinical and biochemical parameters. Observations were subjected to statistical analysis using the descriptive statistics, Pearson’s coefficient of correlation and Multiple regression analysis. PCOS women presented with central adiposity (Waist circumference (cms) - 85.82 ± 12.16 v/s 78.84 ± 9.66p Conclusion: Obesity, IR, high pro-thrombotic and pro-inflammatory factors in Indian PCOS women indicate strong CVD risk and could cause cardiovascular complications in later life. Key words: Dyslipidemia, fibrinogen, HDL2c, hs-CRP, Insulin resistance, PCOS, sd LDLc.

Metabolic syndrome (MS) is found to be more prevalent in patients with psychiatric disorders including depression. This study aimed to assess the association of inflammatory and liver markers with cardiometabolic risk factors in patients with Depressive disorders. Prevalence of MS by using Modified NCEP ATP-III Criteria and liver enzymes and CRP were assessed in 382 patients with depressive disorders. MS prevalence was 27.7% and lower HDL level was the commonest metabolic abnormality. ALT, GGT, and CRP levels were positively correlated with weight and BMI. ALT, GGT, and CRP levels were significantly greater in patients with abnormal waist circumference, triglyceride levels and raised blood pressure, compared to patients with normal indices. Such association was not found with abnormal HDL cholesterol and hyperglycemia. Levels of GGT and CRP were significantly greater in patients with MS compared to patients without MS and CRP was significant predictor for MS. To conclude, one-fourth of depressed patients had MS. MS and metabolic abnormalities were associated with inflammatory marker and liver enzymes. Patients with depression should be regularly evaluated for cardiovascular risk factors, liver enzymes, and inflammatory markers.

The aim was to evaluate the CVD risk in type 2 diabetes mellitus subjects on diagnosis using the traditional lipid profile and apo-proteins B and A1 in correlation with serum insulin and IR. The study was conducted on 280 subjects (100 Controls and 180 type 2 DM subjects) who first reported to our OPDs. We analysed FBG, serum Insulin, HOMA – IR, Lipid profile and apo –B and A1. There was a female preponderance, obesity, hyperinsulinemia, insulin resistance (IR) and diabetic dyslipidaemia (hypertriglyceridemia and reduced HDLc). Correlative analysis of BMI showed significant correlation with SBP, lipid profile (except HDLc) and apo –B. Similarly correlative analysis of serum insulin and HOMA –IR showed significant correlation with FBG, lipid profile (except HDLc with HOMA –IR which was Non – significant) and apo –B. CVD risk ratios T. Chol./HDLc and apo –B/apo –A1 showed a significant association with serum insulin and HOMA – IR. Type 2 diabetics from Western Rajasthan, especially those with high BMI, are at increased risk of complications due to atherosclerosis. The positive association of the two CVD risk ratios with serum insulin and IR showed that type 2 diabetics’ risk of developing CVD increases with rise in serum insulin and IR.

Background: There is a gross dearth of correlative data for cardiovascular diseases. Aim: We aimed to explore the association of systolic and diastolic blood pressure with anthropometric and biochemical parameters of hypothyroid patients in order to establish any correlation that may exist and be useful in an early diagnosis and management against cardiovascular risk. Materials and Methods: The study included 100 healthy controls and 150 newly diagnosed hypothyroid patients. Subjects were evaluated anthropometrically and biochemically for fasting blood sugar, triiodothyronine, thyroxine, thyroid stimulating hormone, Insulin, C-peptide, lipid profile, apo-B and apo-A 1 . The results were statistically analysed using unpaired t-test and Spearman's coefficient of Correlation. Results: The hypothyroids had a female preponderance (73.3%) however; their biochemical profiles were comparable with those of male counterparts. They had raised Body Mass Index, hypertension, hyperinsulinemia, insulin resistance, raised C-peptide, dyslipidaemia with raised apo-B and reduced apo-A 1 and strong association of systolic and diastolic blood pressure with insulin, insulin resistance, C-peptide and Total cholesterol/HDLc (TC/HDLc). Conclusion: Strong association of hypertension with serum insulin, IR, C -peptide and TC/HDLc hints significant contribution towards cardiovascular risk in hypothyroid adults of Jodhpur.

Type V hypertriglyceridemia in children is a rare condition since it has often been associated with obesity, type II diabetes, metabolic syndrome and hormone therapy. We encountered a case of massive hypertriglyceridemia (1900 mg/dl) in a 6 years old boy with complains of acute pancreatitis but no physical manifestations. There was no family history of sudden cardiac death, father and younger male sibling were found to be normal. The mother however had hypertriglyceridemia. The child was managed by dietary changes, omega 3 capsules and low dose fenofibrate. On follow up showed there was reduction in lipid profile and lipoprotein electrophoretic pattern showed bands for VLDL and chylomicron indicating type V hyperlipidemia. Early diagnosis via screening for lipid profile of such patients and their family can improve prognosis and quality of life of these children.

Microalbuminuria is an established cardiovascular risk indicator in diabetes, hypertension and the general population. There is lack of information on MAU in healthy obese Indian adults and an ongoing debate whether obese adults deserve targeted identification and clinical intervention for MAU and prediabetes. We aimed to screen the healthy obese, young (group I) and middle aged (group II) adults for prevalence of MAU and prediabetes and study its association with Framingham risk score. The study included 50 healthy obese young (20-30 years) and middle aged adults (31-50 years), attending the outpatient clinic of Dept. of Medicine for a duration of 2 months (July-August). The patients were screened for fasting blood sugar, lipid profile and MAU. Of the total patients 28 % had MAU, 32.14 % of which had prediabetes and 33.33 % had diabetes whereas 10 % were normoglycemic. The group I patients had 50 % cases of MAU and group II had 25 % patients with MAU. Group II 63.63 % pre-diabetics. The values of MAU obtained were correlated with age, gender, body mass index, systolic and diastolic blood pressure, FBS, waist to hip ratio using Pearson's Coefficient (p

Cardiovascular disease (CVD) is the leading cause of mortality all over the world. However, majority of CVDs are caused by risk factors that can be controlled, treated or modified, such as hypertension, cholesterol, overweight/obesity, tobacco use, sedentary lifestyles and diabetes. Various environmental toxicants like Lead (Pb) are also important preventable causes of variation in CVDs as reported in different human populations [1]. Although important measures have already been implemented in a number of countries to reduce environmental Pb exposure which includes the use of unleaded gasoline, Pb free paints, solder of canned foods, and glazed ceramics used for storage and preparation of food, it is still a major environmental health hazard in specific communities and targeted high-risk populations [2]. Pb intoxication has been found to be associated with hypertension and promotes atherosclerosis in experimental animals [2, 3]. Hypertensive effects of Pb has also been documented in workers chronically exposed to high Pb levels [4]. Several epidemiological and clinical studies have found a link between chronic Pb exposure and elevated blood pressure [1]. Although a dose–response relationship between Pb exposure and blood pressure has also been reported however shape of the dose response relationship is not completely elucidated, especially at low levels of exposure. It is still not clear what should be the lowest level of Pb exposure that shall not be associated with Pb toxicity and its impact on blood pressure, although in the available studies there seems to be no evidence of a threshold effect [5]. The precise mechanisms explaining a hypertensive effect of low chronic exposure to environmental Pb are unknown. Muntner et al. [6] has reported an inverse association between estimated glomerular filtration rate and blood Pb level at Pb concentration below 5 μg/dl in general population studies, indicating that Pb-induced reductions in renal function could play a major role in hypertension. Enhanced oxidative stress, down-regulation of nitric oxide, stimulation of the renin-angiotensin system and soluble guanylate cyclase are among other potential mechanisms which could result in increased vascular tone and peripheral vascular resistance [5]. Metal-mediated formation of free radicals may enhance lipid peroxidation and changes in calcium and sulfhydryl homeostasis. Pb by promoting the production of reactive oxygen species, triggers a cycle of oxidative stress and inflammation in target tissues. Depletion of sulfhydryl reserves in cells provides an indirect mechanism for redox-inactive metals induced oxidative stress. These findings suggest a possible involvement of oxidative stress in the pathophysiology of Pb toxicity. Although oxidative stress is one of the important factor in the pathophysiology of Pb toxicity, it is not clear whether these alterations are the cause of the oxidative damage or a consequence of it. Increased expression and production of inflammatory markers in association with Pb exposure have also been reported in humans [2]. Most of the data available have been drawn from experimental studies and there are few cohort studies that evaluate the association of Pb with clinical cardiovascular outcomes in general population settings. The National Health and Nutrition Examination Surveys (NHANES) II and III showed a statistically significant increase in cardiovascular mortality with increasing blood Pb levels, although there was an overall decline in Pb levels in the US adults. Similarly the British Regional Heart study showed positive but non-significant association of coronary heart disease or stroke with elevated Pb levels. However, the unresolved issue is the impact of uncontrolled confounding and measurement error on the relative risk estimates in studies of Pb and clinical cardiovascular end points. Similarly the validity of occupational studies on Pb and cardiovascular mortality is limited by different methodological problems like bias of observations in occupationally exposed workers, which cannot be extrapolated to general population [5]. Various factors, both conventional and novel risk factors have been shown to be responsible for the morbidity and mortality of patients with cardiovascular diseases. No attention has so far been given to environmental toxicants and other trace elements such as Pb, which can exacerbate the disease condition. A prospective pro-atherogenic effect, even if modest compared to other conventional risk factors would have a significant impact in sensitive population groups. In view of this it becomes important to explore the precise role and mechanism of Pb in development of atherosclerosis and CVD.

Metabolic syndrome or MS as it is called is a compilation of most of the non-communicable disease components which is a life style disease with strong genetic predisposition, culminating in a morbid adulthood. The increasing number of subjects under the umbrella of MS is alarming. Diabetes mellitus, hypertension is the end result of this insulin resistance as it is sometimes called. Apart from genes, it also has strong inflammatory components that are responsible for early onset of MS. MS is marked by a gamut of inflammatory and non-inflammatory markers. If diagnosed early by screening the population, the percentage of florid cases of this debilitating syndrome can be brought down. Active intervention and constant monitoring of affected or predisposed young subjects will curtail the progress of MS and prevent full blown diabetes and hypertension, thus reducing cardiovascular complications, other morbidity and early mortality. Prevention is always better than cure.

Aim: We aimed to diagnose latent diabetic hypothyroid patients presenting with symptoms of metabolic syndrome (MS) based on the Adult Treatment Panel-III (ATP-III) guidelines. Background: Type 2 diabetes mellitus (DM) coexisting with thyroid disorders is difficult to manage. With an ever-increasing incidence of both these disorders and an increasing risk of secondary complications due to their coexistence, newer correlative studies are needed for the early diagnosis of these diseases. Subjects and Methods: The present study was conducted on 100 healthy controls and 150 newly diagnosed hypothyroid patients. The patients were selected based on symptomatology and thyroid function tests. They were then analyzed for body mass index (BMI), blood pressure, fasting blood sugar (FBS), fasting serum insulin, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and apolipoprotein B (apo-B) and apolipoprotein (apo-A 1 ). Statistical Analysis: Analysis was done using the Students t test and Spearman's coefficient of correlation. Results: For hypothyroid patients who presented with raised BMI, diastolic hypertension and dyslipidemia were further investigated for underlying latent diabetes. Of the total hypothyroid patients, 53.3% had raised FBS, 48% had diastolic hypertension, 86.6% had hypertriglyceridemia and 66.67% patients fulfilled three conditions for MS as per the ATP-III guidelines. There was highly significant correlation of serum insulin and HOMA-IR with lipid fractions and cardiovascular disease (CVD) risk ratios (total cholesterol/high-density lipoprotein cholesterol) and apo-B/apo-A 1 in hypothyroid patients. Conclusion: All hypothyroid patients should be closely watched for presence of DM and MS for prevention of atherogenic dyslipidemia, which may lead to CVDs. The estimation of serum insulin, apo-A 1 and apo-B, along with the traditional lipid profile may be useful in such patients.

Aim: We aimed at evaluating the cardiovascular disease (CVD) risk of thyroid disorder patients at diagnosis, using the traditional lipid profile, apo-B and apo-A1 in correlation with serum insulin and insulin resistance (IR) and C-peptide. Background: With an ever increasing incidence of CVD in most urban populations, there has been a demand for newer techniques that could help in the early detection of the risk of this disease complex. Materials and Methods: The present study was conducted on 100 healthy controls and 150 hypothyroid and 70 hyperthyroid patients, coming for the first time to our OPDs. The patients were selected on the basis of symptomatology and serum T3, T4, thyroid stimulating hormone (TSH) evaluations. They were then analyzed for body mass index (BMI), blood pressure (BP), serum insulin, homeostasis model assessment-insulin resistance (HOMA-IR), C-peptide, lipid profile and apo-B and -A1. Statistical analysis was done using Student's “t” test and Spearman's coefficient of correlation. Results: The hypothyroid patients presented with high BMI, diastolic hypertension, dyslipidemia, hyperinsulinemia, IR and raised serum C-peptide. There was highly significant correlation of serum insulin, HOMA-IR and C-peptide with lipid fractions and CVD risk ratios, T. chol/HDLc and apo-B/apo-A1, in hypothyroid patients. The hyperthyroid patients presented with systolic hypertension and a significant correlation of T. chol/HDLc with HOMA-IR. Hyperthyroid patients also had hyperinsulinemia, but reduced serum C-peptide levels. Conclusion: We conclude that the estimation of traditional lipid profile along with serum insulin, IR, C-peptide, apo-A1 and apo-B would not only help assess the thyroid status, but can also help in the early evaluation of a possible risk of CVD.